摘要
本研究旨在观察丹酚酸B对脑缺血再灌注损伤大鼠血脑屏障的影响,探讨其可能的作用机制。研究采用线栓法阻塞大鼠大脑中动脉,并于缺血后2 h进行再灌注,造成脑缺血再灌注损伤,用免疫组织化学法检测缺血侧脑血管周围免疫球蛋白IgG的渗出以及MMP-9(基质金属蛋白酶-9)和NOS2(一氧化氮合酶2)的表达,用Western blotting方法检测p-p38和p-ERK1/2蛋白含量变化。结果显示,手术后第2天缺血再灌注组损伤侧脑血管周围免疫球蛋白IgG的渗出增加,表明血脑屏障功能破坏,脑组织中MMP-9和NOS2表达增加,同时p-p38和p-ERK1/2含量也明显增加。手术后第7天,缺血再灌注组脑组织中MMP-9及NOS2依然维持在同手术后第2天接近的高水平,p-p38含量高于手术后第2天,p-ERK1/2含量略低于手术后第2天。丹酚酸B(1和10 mg.kg?1)能够明显改善缺血再灌注引起IgG的渗出增加(P<0.05),同时MMP-9和NOS2表达也明显抑制(P<0.05)。丹酚酸B(10 mg.kg?1)能够显著降低手术后第2天和第7天p-p38和p-ERK1/2蛋白含量(P<0.05)。丹酚酸B(1 mg.kg?1)在手术后第7天能显著减少p-p38的含量(P<0.05)。以上结果表明,丹酚酸B的血脑屏障保护作用可能与抑制MMP-9激活相关,其中丹酚酸B抑制MAPK通路可能起重要作用。
The aim of the study is to investigate the effect of salvianolic acid B（SalB） on blood-brain barrier（BBB） in rats after cerebral ischemia-reperfusion,and to illustrate its possible mechanisms.Cerebral ischemia-reperfusion was induced by middle cerebral artery occlusion in rats.The break-down of BBB was indicated by extravasations of immunoglobulin（IgG） monitored with immunohistochemistry.The expression of MMP-9 and NOS2 in the brain was determined by immunohistochemistry,and the expression of p-p38 and p-ERK1/2 was detected by Western blotting.It was shown that on day 2 after ischemia-reperfusion the IgG accumulated around the vascular boundary zone,suggesting the break-down of BBB,and the expression of MMP-9 and NOS2 up-regulated at the same time.The result of Western blotting suggested that the expression of p-p38 and p-ERK1/2 increased.On day 7 after ischemia-reperfusion the expression of MMP-9 and NOS2 was about the same level as day 2,the expression of p-p38 was higher than that on day 2 and the expression of p-ERK1/2 was slightly lower than that on day 2.SalB（1 and 10 mg.kg？1） significantly alleviated the extravasations of immunoglobulin induced by cerebral ischemia-reperfusion（P 0.05）.On day 2 and day 7 SalB attenuated the expression of MMP-9 and NOS2（P 0.05）.SalB（10 mg.kg？1） reduced the expression of p-p38 and p-ERK1/2 apparently on day 2 and 7 after ischemia-reperfusion（P 0.05）.SalB（1 mg.kg？1） inhibited the expression of p-p38 on day 7 after ischemia-reperfusion（P 0.05）.The results indicate that SalB protects blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting the MAPK pathway.
出处
《药学学报》
CAS
CSCD
北大核心
2010年第12期1485-1490,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(30772763)
教育部创新团队发展计划项目(IRT0810)
教育部留学回国人员基金
关键词
丹酚酸B
脑缺血再灌注
血脑屏障
MAPK通路
salvianolic acid B
cerebral ischemia-reperfusion
blood-brain barrier
MAPK pathway
